Exposure of zebrafish larvae to bisphenol A, bisphenol S, di-(2-ethylhexyl) phthalate, and di-(2-ethylhexyl) adipate induces oxidative stress, resulting in hepatotoxicity and disruption in lipid metabolism.

Abstract

Bisphenol A (BPA), bisphenol S (BPS), di-(2-ethylhexyl) phthalate (DEHP), and di-(2-ethylhexyl) adipate (DEHA) are commonly used in plastic materials. Liver and lipid metabolism have been identified as being affected by these compounds but are primarily limited to rodents. In this study, hepatotoxicity and disruption in lipid metabolism of BPA, BPS, DEHP, and DEHA were assessed using zebrafish larvae as a model. After 96 h of exposure to BPA (0.13 ~ 1314 nM), BPS (0.11 ~ 1198 nM), DEHP (0.07 ~ 768 nM), and DEHA (0.08 ~ 809 nM) of test chemicals in water, zebrafish embryos were assessed for survival, growth, activities of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), triglyceride (TG) level, reactive oxidative stress (ROS), and transcription of genes related to peroxisome proliferator-activated receptor (PPAR), endoplasmic reticulum stress, and antioxidant enzymes. Growth retardation and significant increase in ALT and AST were observed in zebrafish larvae exposed to BPA, BPS, DEHP, and DEHA. Exposure to the test chemicals significantly increased ROS and the expression of chop, xbp1, eif2a, sod1, cat, and gpx1a genes. Pretreatment with N-acetylcysteine, one of the representative antioxidants, alleviated ALT and TG induced by the tested chemicals. Our results showed that BPA, DEHP and their substituted compounds caused oxidative stress and adversely affected the liver and lipid metabolism in zebrafish, leading to growth retardation. The results may provide new insights into the risk management of bisphenols and phthalates alternatives to aquatic organisms.